Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression
| العنوان: | Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression |
|---|---|
| المؤلفون: | Qing Feng Yang, Ofer Eidelman, Clifton L. Dalgard, Bette S. Pollard, Harvey B. Pollard, Catherine Jozwik, Meera Srivastava |
| المصدر: | Journal of Carcinogenesis Journal of Carcinogenesis, Vol 12, Iss 1, Pp 8-8 (2013) |
| بيانات النشر: | Medknow Publications & Media Pvt Ltd, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Gene isoform, Cancer Research, medicine.medical_specialty, Digitoxin, Health, Toxicology and Mutagenesis, Caspase 3, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, polycyclic compounds, 030304 developmental biology, Cardiac glycoside, 0303 health sciences, Cardiac glycosides, business.industry, NFAT, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Chromatin, Cell biology, carbohydrates (lipids), Endocrinology, c-MYC, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Cancer cell, Original Article, business, nuclear factor of activated T-cells, medicine.drug |
| الوصف: | Background : Cardiac glycosides such as digitoxin have been shown to directly cause apoptotic death of cancer cells both in vitro, and in vivo. However, the mechanism connecting cardiac glycoside action to apoptosis is not known. It has been reported that compounds resembling digitoxin are able to reduce c-MYC expression. Furthermore, it has been previously shown that the transcription of c-MYC depends on nuclear factor of activated T-cells (NFAT) binding sites in the c-MYC promoter. We have therefore hypothesized that NFAT might mediate digitoxin effects on c-MYC mRNA message. Materials and Methods : We have chosen to study this process in HeLa cells where structurally intact c-MYC genes in 8q24 co-localize with human papilloma virus 18 at all integration sites. Results : Here we show that within the 1 st h following treatment with digitoxin, a significant reduction in c-MYC mRNA occurs. This is followed by a precipitous loss of c-MYC protein, activation of caspase 3, and subsequent apoptotic cell death. To test the NFAT-dependence mechanism, we analyzed the effects of digitoxin on NFAT isoform-dependent auto-activation of a NFAT-luciferase expression system. Drug dependent effects on expression varied according to each of the four canonical NFAT isoforms (1, 2, 3 or 4). The most digitoxin-sensitive NFAT isoform was NFAT1. Using c-MYC chromatin immune precipitation, we find that digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter. Conclusions : These results suggest that the carcinotoxic activity of digitoxin includes suppression of NFAT-driven c-MYC expression. |
| اللغة: | English |
| تدمد: | 1477-3163 0974-6773 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e27b2cddaa44d939792ad9b21295576e http://europepmc.org/articles/PMC3709410 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e27b2cddaa44d939792ad9b21295576e |
| قاعدة البيانات: | OpenAIRE |
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